PhysioNet, established in 1999 as the NIH-sponsored Research Resource for Complex Physiologic Signals, has attained a preeminent status among data and software resources in biomedicine. Its data archive, PhysioBank, was the first, and remains the world's largest, most comprehensive and most widely used repository of time-varying physiologic signals. Its software collection, PhysioToolkit, supports exploration and quantitative analyses of PhysioBank and similar data with a wide range of well-documented, rigorously tested, open-source software that can be run on any platform. PhysioNet's team of researchers leverages results of other funded projects to drive the creation and enrichment of: Data collections that provide increasingly comprehensive, multifaceted views of pathophysiology over long time intervals, such as the MIMIC II (Multiparameter Monitoring in Intensive Care) Database of critical care patients; Analytic methods that lead to more timely and accurate diagnoses (such as prediction of acute hypotensive events), and elucidation of dynamical changes associated with disease and aging (such as cardiopulmonary interactions during sleep disordered breathing syndrome); User interfaces, reference materials and services that add value and improve accessibility to PhysioNet's data and software (such as PhysioNetWorks, a virtual laboratory for data sharing). Impact: PhysioNet is a proven enabler and accelerator of innovative research by specialists, young investigators and trainees alike, working on independent projects and focused biomedical engineering challenges made possible by data that are inaccessible otherwise. Through its PhysioNetWorks, the Resource gives researchers new tools and the opportunity not merely to meet NIH data sharing mandates, but to enrich the data commons with accessible, valuable contributions. By providing free access to its unique and wide- ranging data and software collections, PhysioNet enables studies that lead to an average of 70 scholarly publications per month (well over 5000 studies since its inception by academic, clinical, and industry-affiliated researchers worldwide. Specific aims: For the next 5 years we aim to: 1. Accelerate PhysioNet's growth with new technology and data; 2. Drive relevant innovation through a vigorous research program on complex physiologic signals; 3. Stimulate and challenge a growing community of investigators.